ABSTRACT
The development of adverse drug reactions (ADRs) induced by xenobiotics and other substances is a complex process starting from initial interactions with chemical or biological agents, via pharmacological and physiological pathways, to early biological and pathological effects, and then to clinical effects and events. Park et al. (1998) classified ADRs, from clinical and pharmacopathological perspectives, into five types based on their mechanisms, frequency, predictability, and pharmacological actions. Type A includes ADRs that are predictable from known pharmacology, often representing an aggregation of primary and/or secondary pharmacological effects of an agent. These ADRs are usually dose-dependent and can be alleviated through dose reduction or removal of the agent, with hemorrhage caused by anticoagulants as one such example. Type B consists of ADRs which are believed to be metabolically and/or immunologically mediated and for which individual susceptibility factors that have not been fully understood may play an important role. These reactions are less common than those in Type A, and usually tend to be more serious, and account for many drug-induced mortalities, e.g., anaphylaxis, halothane hepatitis. Type C consists of ADRs whose biological characteristics can be predicted from the structure of the agent including its metabolites, as in acetaminophen (paracetamol) hepatotoxicity. Type D consists of ADRs that occur many years after initial interaction with the agent; examples include secondary tumors induced by chemotherapeutic agents and teratogenic effects (e.g., thalidomide with limb abnormalities and malformations of other organs including congenital heart disease). ADRs of type E, though uncommon, are drug withdrawal effects, e.g., myocardial ischemia after β-blocker withdrawal.
